key: cord-0919262-m8z4wsm6
authors: Shakeri, Habibesadat; Azimian, Amir; Ghasemzadeh‐Moghaddam, Hamed; Safdari, Mohammadreza; Haresabadi, Mehdi; Daneshmand, Tahereh; Namdar Ahmadabad, Hasan
title: Evaluation of the relationship between serum levels of zinc, vitamin B12, vitamin D, and clinical outcomes in patients with COVID‐19
date: 2021-08-21
journal: J Med Virol
DOI: 10.1002/jmv.27277
sha: 86a099a422de7eb5f4a22d7ad4505745221e30a3
doc_id: 919262
cord_uid: m8z4wsm6

Due to the known anti‐inflammatory and antiviral effects of zinc, 25(OH)D, and vitamin B12, in this study, we explored the association between serum levels of these micronutrients in coronavirus disease 2019 (COVID‐19) patients at the time of admission and the clinical outcomes. This study was carried out on 293 patients with COVID‐19, who were hospitalized at Imam Hassan hospital (Bojnourd, Iran). We collected demographic data, clinical characteristics, values of serum biochemical parameters in the first week of admission, and clinical outcomes from electronic medical records. We also measured serum levels of zinc, 25(OH)D, and vitamin B12 within 3 days of admission. Of the 293 hospitalized, the median age was 53 years, and 147 (50.17%) were female. Thirty‐seven patients (12.62%) were admitted to the intensive care unit (ICU), and forty‐two (14.32%) died. We found that the serum levels of zinc, vitamin B12, and 25(OH)D were lower in patients who died than those who were admitted to ICU or non‐ICU and survived; however, these differences were not statistically significant for vitamin B12 and 25(OH)D (p > 0.05). The serum concentrations of zinc, vitamin B12, and 25(OH)D at the time of admission did not affect the length of hospital stay in patients with COVID‐19. In general, it seems that serum levels of 25(OH)D, vitamin B12, and especially zinc at the time of admission can affect clinical outcomes in COVID‐19 patients.

The coronavirus disease 2019 that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a clinical threat worldwide. 1 This infection mostly presents with mild flu-like symptoms, but some patients, especially older individuals and those with underlying illnesses, evolve into critical conditions and rapidly develop acute respiratory distress syndrome, respiratory failure, multiple organ disorder, and death. 2, 3 The severe forms of the disease are accompanied by an aggressive inflammatory response with the typical characteristics of an uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines by immune cells known as "cytokine storm." 4 It has been reported that the severity of COVID-19 can be influenced by various factors such as age, sex, race, current health issue, and nutritional status. 3, 5 Micronutrients include vitamins (e.g., A, B, and D) and minerals (e.g., Ca, P, and Mg), as well as trace elements (Zn, CU, and Fe) involved in initiating, maintaining, and regulating host immune reactions to the virus infections through the effect on frequency and function of innate and adaptive immune cells, production and development of virus-specific antibodies, production of pro-, and antiinflammatory cytokines, oxidative burst reaction, and so forth. 6, 7 Zinc is an essential micronutrient with potent immunoregulatory and antiviral properties that is involved in the growth and the maturation of immune cells, development and activation of lymphoid cells, regulation of inflammatory cytokines, and controlling oxidative stress. 8 Zinc deficiency is associated with immune system dysfunction, neurosensory disorders, decreased body mass, enhanced risk of inflammatory disorders, increased risk of incidence, and morbidity of viral pneumonia. 7 It is well recognized that vitamin D as an essential mediator of immune responses, has anti-infective, anti-inflammatory, and immunomodulant functions. It can modulate immune responses to viral respiratory tract infection and improve lung function through the reduction of inflammation. 6 Vitamin B12 as an immunomodulator can regulate cellular immune responses and can also support hematopoiesis. 9 Reduced number of lymphocytes, suppression of NK cell activity, and decreased CD8+ cells were found in humans with vitamin B12 deficiency. 6 A previous study also showed that vitamin B12 could suppress viral replication in the host cells. 7 It is now well established that insufficiency or deficiency of micronutrients such as serum 25(OH)D, vitamin B12, and zinc can affect host immune responses to viral infections, inflammatory activity, and finally influence clinical outcome in patients with COVID-19. [10] [11] [12] [13] Although serum levels of zinc, 25(OH)D, and vitamin B12 were groups, although these differences were not statistically significant (p = 0.21) (Figure 1 ).

It can be seen from the data in Table 2 we observed that serum 25 (OH)D levels in patients who did not need intubation were significantly higher than those who needed intubation (p = 0.006), while we did not find these significant differences in zinc and vitamin B12 ( Table 2 ).

In the current study, we registered demographic data and clinical characteristics of COVID-19 patients and found the most common symptoms and frequency of comorbidities of COVID-19 patients were similar to those in prior literature. 2, 14 The European Food Safety Authority believes six vitamins (D, A, C, Folate, B6, and B12) and four minerals (zinc, iron, copper, and selenium) to be essential for the normal functioning of the immune system against infections. 15 Due to the known anti-inflammatory and antiviral effects of zinc, 25(OH)D, and vitamin B12, in this study, we explored serum levels of these micronutrients in patients with COVID-19 at the time of hospitalization. We also investigated the association between their serum levels and clinical outcomes.

In the present study, serum levels of zinc and 25(OH)D observed in COVID-19 patients are higher than those observed by Im et al., 10 while the measured values for vitamin B12 are lower. These differences may be affected by the sample size, age, race, sex ratio, geographical location, and so forth. Consistent with this possibility, we showed that serum levels of vitamin D are closely related to sex and age. 16 Comparative analysis showed that serum zinc levels were significantly lower in patients who died than in those who were admitted to ICU or non-ICU and survived (Figure 1 ). Following the present results, Jothimani et al. 13 showed decreased serum levels of zinc increase the mortality rate in COVID-19 patients. However, their finding of the association between serum zinc levels and length of hospital stay was contrary to the present study. 13 In a meta-analysis, It has previously been observed that vitamin D can protect against respiratory tract infections and reduce the risk of acute respiratory infections. 7 In the current study, we found that serum levels of 25(OH)D in the death group are lower than those of ICU and non-ICU admission groups, although these differences were not Note: Data are the mean ± SD. *p < 0.05 was considered statistically significant.

Abbreviations: COVID-19, coronavirus disease 2019; SD, standard deviation. statistically significant (Figure 1 ). This finding is consistent with that of Pizzini et al. 20 Regulation of antimicrobial proteins expression, inhibition of T cell proliferation, reduction of expression of pro-inflammatory cytokines, and promotion of phagocytic ability of macrophages were proposed as the underlying mechanism of action vitamin D in COVID-19 patients. 12 We also observed that serum 25 (OH)D levels in patients who did not the need for intubation significantly higher 

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The authors declare that there are no conflicts of interest.

The author who conceived the study: Habibesadat Shakeri. Authors 

The data that support the findings of this study are available from the corresponding author upon reasonable request.

http://orcid.org/0000-0002-2532-8198Hasan Namdar Ahmadabad https://orcid.org/0000-0002-5640-5440